Use of net reclassification improvement (NRI) method confirms the utility of combined genetic risk score to predict type 2 diabetes.

BACKGROUND: Recent genome-wide association studies (GWAS) identified more than 70 novel loci for type 2 diabetes (T2D), some of which have been widely replicated in Asian populations. In this study, we investigated their individual and combined effects on T2D in a Chinese population. METHODOLOGY: We selected 14 single nucleotide polymorphisms (SNPs) in T2D genes relating to beta-cell function validated in Asian populations and genotyped them in 5882 Chinese T2D patients and 2569 healthy controls. A combined genetic score (CGS) was calculated by summing up the number of risk alleles or weighted by the effect size for each SNP under an additive genetic model. We tested for associations by either logistic or linear regression analysis for T2D and quantitative traits, respectively. The contribution of the CGS for predicting T2D risk was evaluated by receiver operating characteristic (ROC) analysis and net reclassification improvement (NRI). RESULTS: We observed consistent and significant associations of IGF2BP2, WFS1, CDKAL1, SLC30A8, CDKN2A/B, HHEX, TCF7L2 and KCNQ1 (8.5×10(-18)

Psychological factors and subclinical atherosclerosis in postmenopausal Chinese women in Hong Kong.

BACKGROUND: Substantial evidence shows that psychological factors are associated with cardiovascular diseases. However, data on the association between psychological factors and subclinical atherosclerosis is lacking in postmenopausal Chinese women. OBJECTIVES: To examine the associations of perceived stress and trait anxiety with subclinical atherosclerosis in postmenopausal Chinese women in Hong Kong. Their relationships with biological and behavioral risk factors were also examined. METHODS: Between 2002 and 2004, we recruited 518 postmenopausal women aged 50-64 years. Perceived stress and trait anxiety were evaluated by the perceived stress scale and the state-trait anxiety inventory, respectively. Subclinical atherosclerosis was determined by measuring carotid intima-media thickness (IMT) and plaque using B-mode ultrasonography. RESULTS: Perceived stress and trait anxiety showed no significant association with IMT or plaque. Multivariate analyses showed high perceived stress scores were associated with an increased risk of elevated total cholesterol (OR=2.10; 95% CI=1.17-3.77) and elevated low-density lipoprotein cholesterol (LDL-C) (OR=2.39; 95% CI=1.36-4.21). High trait anxiety scores were associated with a 2.7-fold risk of elevated LDL-C (OR=2.74; 95% CI=1.56-4.80). Women with high perceived stress or trait anxiety scores were more likely to be physically inactive. CONCLUSIONS: Perceived stress and trait anxiety were associated with atherogenic lipid levels, but not subclinical atherosclerosis. Maintaining high physical activity may help alleviate psychological stress and anxiety.

Distribution of C-reactive protein and its association with subclinical atherosclerosis in asymptomatic postmenopausal Chinese women.

Substantial evidence shows that C-reactive protein (CRP) is associated with atherosclerosis. However, data on the association between CRP and subclinical atherosclerosis are lacking in postmenopausal Chinese women. We aimed to describe the distribution of CRP and its association with metabolic syndrome (MS) and subclinical atherosclerosis in postmenopausal Chinese women in Hong Kong. Between 2002 and 2004, we recruited 518 postmenopausal women aged 50 to 64 years. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria. Subclinical atherosclerosis was determined by measuring carotid intima-media thickness (IMT) and plaque (focal wall thickening ≥1.5 mm) using high-resolution B-mode ultrasonography. Median CRP level was 1.00 mg/L. Women with MS had higher median CRP levels than those without MS (1.85 vs 0.80 mg/L, P < .05), and there was a modest trend toward increasing CRP levels with more metabolic components (P for trend < .05). Adjusted for age, hormonal use, and lifestyle factors, women with CRP levels of 0.5 to less than 1.0 mg/L had significantly higher mean IMT compared with those with CRP levels of less than 0.5 mg/L (0.78 vs 0.74 mm, P < .05). Odds ratio for plaque was 1.92 (95% confidence interval, 1.06-3.50) for women with CRP levels of 1.0 to less than 3.0 mg/L compared with those with CRP levels of less than 0.5 mg/L. Further adjustment for MS eliminated the associations. C-reactive protein did not add prognostic value to MS in the prediction of subclinical atherosclerosis. Compared with women without MS and who had CRP levels of less than 3.0 mg/L, those with CRP of at least 3.0 mg/L alone had similar IMT levels (0.75 vs 0.74 mm) and prevalence of plaque (19.4% vs 20.0%). Similarly, women with MS and who had CRP levels of at least 3.0 mg/L had similar IMT levels (0.81 vs 0.81 mm) and prevalence of plaque (30.1% vs 29.7%) compared with those with MS alone. C-reactive protein was strongly associated with MS and its individual components. However, it is not an independent predictor of subclinical atherosclerosis in postmenopausal Chinese women.

Carotid atherosclerosis and the risk factors in early postmenopausal Chinese women.

OBJECTIVES: To describe the distribution of intima-media thickness (IMT) and the prevalence of plaque by carotid segments, walls and sides, and to examine their associated risk factors in asymptomatic, early postmenopausal Chinese women in Hong Kong. METHODS: Between 2002 and 2004, the study recruited 518 postmenopausal women aged 50-64 years. They were examined by B-mode ultrasound to measure the IMT and the prevalence of plaque at the near and far walls of common carotid (CCA), bifurcation (bulb), and internal carotid (ICA) of both the left and right carotid arteries. Blood pressures, obesity indices, lipids and glucose levels, sociodemographic, medical and lifestyle factors were also obtained. RESULTS: The mean IMT was 0.76+/-0.12 mm (range: 0.53-1.33 mm). IMT was significantly thicker on the far wall than on the near wall and differed among segments (being thickest at the bulb and the narrowest at the ICA). 21.8% had at least one plaque in the carotid artery with most of the plaque found at the bulb area. Systolic blood pressure had statistically significant relationship with IMT that were fairly homogeneous among different segments. Lipids were associated with the CCA and bulb IMT, but not the ICA IMT. Diabetes predicted only CCA IMT. Older age, higher waist-hip-ratio and low-density lipoprotein cholesterol were significant predictors of plaques at all sites combined. CONCLUSIONS: We described the distribution of IMT and the prevalence of plaque in asymptomatic, early postmenopausal Chinese women. Associations of risk factors with IMT of different arterial segments were also observed.

Association of general and abdominal obesities and metabolic syndrome with subclinical atherosclerosis in asymptomatic Chinese postmenopausal women.

OBJECTIVE: This study aimed to investigate the relationships between obesity, especially abdominal obesity, andmetabolic syndrome (MS) with carotid intima-media thickness (IMT) and plaque, markers of subclinical atherosclerosis, in asymptomatic Chinese postmenopausal women in Hong Kong. DESIGN: A total of 518 postmenopausal women aged 50 to 64 years were recruited through random telephone dialing. Body mass index (BMI), waist circumference, waist-to-hip ratio, sociodemographic characteristics, blood pressures, medical, biochemical and lifestyle factors were obtained. MS was defined on the basis of the National Cholesterol and Education Program, Adult Treatment Panel III criteria. Subclinical atherosclerosis was determined by measuring IMT and plaque using high-resolution B-mode ultrasonography. RESULTS: Women with a BMI of 25 kg/mor greater, a waist circumference of 80 cm or greater, a waist-to-hip ratio of 0.85 or greater, or MS were observed to have higher IMT values and prevalence of plaque. Multivariate analyses revealed that waist circumference was significantly associated with IMT independent of age, hormone therapy, lifestyle and sociodemographic factors, and BMI (P < 0.05), whereas a waist-to-hip ratio of 0.85 or greater was significantly associated with plaque (odds ratio = 1.7; 95% CI: 1.0-2.8) after controlling for age, hormone therapy, lifestyle and sociodemographic factors, BMI, and the traditional cardiovascular risk factors. MS was also associated with IMT after adjustment for age, hormone therapy, lifestyle and sociodemographic factors, and BMI (P < 0.05), whereas its association with plaque was also significant (odds ratio = 1.7; 95% CI: 1.0-2.6) after controlling for age. CONCLUSIONS: Abdominal obesity and MS are independent of general obesity markers of subclinical atherosclerosis in Chinese postmenopausal women.

Soy isoflavone supplementation and fasting serum glucose and lipid profile among postmenopausal Chinese women: a double-blind, randomized, placebo-controlled trial.

OBJECTIVE: Long-term effects of soy-derived isoflavones on lipids remain uncertain, and few data are available on their effects on glycemic control. We examined the effects of isolated soy germ isoflavones on the changes in fasting glucose (FG) and lipids. DESIGN: A double-blind, randomized, placebo-controlled trial was conducted in 203 postmenopausal Chinese women aged 48 to 62 years. They were randomly assigned to receive daily doses of 500 mg calcium, and 0 mg isoflavones (placebo, n=67), 40 mg isoflavones (n=68), and 80 mg isoflavones (n=68). Serum FG, triglycerides, high-density lipoprotein, low-density lipoprotein, total cholesterol, and lipoprotein cholesterol were measured at baseline and 1 year after treatment. The primary data analysis was performed on the 203 randomized women according to the intent-to-treat principle. The last value carried forward was used for any missing data at follow-up. RESULTS: We observed moderate but significant favorable effects of soy isoflavones on the changes (P=0.012) and percentage of changes (P=0.031) in FG (analysis of variance). The 1-year mean (SD) differences of FG changes were -5.2 (-9.4 to -1.0) mg/dL (P=0.010) and -3.3 (-7.5 to 0.9) mg/dL (P=0.18) in the 40- and 80-mg isoflavone groups compared with the placebo group. We also noted a significant interaction between the treatment and baseline FG on the changes in FG (P=0.004). The isoflavone effects were much more significant in women with baseline FG 100 mg/dL or more than in those with FG less than 90 mg/dL. We observed little effect of soy isoflavones on changes in serum lipids among the treatment groups. CONCLUSIONS: One-year of soy isoflavone supplementation might have a favorable effect on FG in women, but has no significant effect on serum lipids.

Effects of soy isoflavone supplementation on cognitive function in Chinese postmenopausal women: a double-blind, randomized, controlled trial.

OBJECTIVE: To investigate whether soy-derived isoflavone extract improves performance in cognitive function and quality of life in Chinese postmenopausal women. DESIGN: The study was a 6-month double-blind, randomized, placebo-controlled, parallel group trial. Participants were community-dwelling women aged 55 to 76 years; 191 eligible women were randomly assigned to receive a daily oral intake of 80 mg soy-derived isoflavones or an identical-appearing placebo for 6 months. Standardized neuropsychological tests of memory, executive function, attention, motor control, language, and visual perception and a global cognitive function assessment were administered face-to-face individually at baseline and at 6-months posttreatment. The validated Chinese version of the Short Form-36 was used for quality of life measurements. RESULTS: Of the participants, 88% (168 women: 80 among the supplementation group and 88 among the placebo group) completed the trial. Intention-to-treat analysis, conducted for 176 participants with 6-month assessment results, revealed no significant differences in outcome measures between treatment groups. Subgroup analysis among the good compliers only (consumed at least 80% of the supplements or placebo; n = 168) and among the age groups younger or older than 65 years also indicated no significant differences for any outcome measures. Types of complaints of adverse events were similar in both treatment groups and included mainly gastrointestinal and musculoskeletal problems. CONCLUSIONS: This 6-month trial indicates that 80-mg soy-derived isoflavone supplementation did not improve performance on standard neuropsychological tests and overall quality of life in generally healthy Chinese postmenopausal women.

Calcium absorption in postmenopausal Chinese women: a randomized crossover intervention study.

The Ca intake and food sources of Chinese postmenopausal women are quite different from those of their Western counterparts. But, little information on Ca metabolism is available in Chinese populations. We determined true fractional calcium absorption (TFCA), true Ca absorption(= TFCA x Ca intake, Va), urinary Ca excretion (Vu,) and the difference between Va and Vu, (Va-u), in response to three dietary Ca intake levels. Twenty-one healthy postmenopausal Chinese women aged 49-64 years were recruited for this randomized crossover trial from a general community, Guangzhou, China. Subjects were randomly assigned to receive 0, 500 and 1000 mg Ca/d for 5 weeks separated by 2-week washout periods. TFCA using Ca stable isotopes, total urinary Ca excretion and Ca intake were determined after 4 weeks of adaptation. Mean values for total Ca intake (Vi) of the three phases were 391 (SD 197), 880 (SD 130) and 1382 (SD 160) mg/d. On usual diet, TFCA, Vu, Va, and Va-u were 0.57 (SD 0.12), 175 (SD 59) mg/d, 216 (SD 98) mg/d and 41 (SD 99) mg/d, respectively. With the supplementations of 500 and 1000 mg Ca/d, TFCAsignificantly decreased to 0.52 (SD 0.12) and 0.43 (SD 0.13) (P<0.001); whereas urinary Ca (P=0.003), Va and Va-u increased significantly (P< 0.001). Using a mixed-effects nonlinear regression model, it was estimated that Va-u was approaching a plateau when mean Ca intake reached 1300 mg/d. In conclusion, the present findings suggest postmenopausal Chinese women have high Ca absorption efficiency and a mean Ca intake of about 1300 mg/d is required to maximize the Va-u.

Greater fruit and vegetable intake is associated with increased bone mass among postmenopausal Chinese women.

Although studies in Caucasian populations have reported the beneficial effects of intakes of fruit and vegetables on bone mass, limited data are available in the Asian populations. We examined the association of the intake of fruits and vegetables with bone mineral density (BMD) in a population-based cross-sectional study of 670 postmenopausal Chinese women aged 48-63 years. Habitual dietary intakes were assessed using a food frequency questionnaire. BMD at the whole body, lumbar spine and left hip were measured with dual-energy X-ray absorptiometry. Univariate regression analyses showed that the total intake of fruits and vegetables was significantly associated with greater BMD at the whole body, lumbar spine (L1-L4), total hip, trochanter and intertrochanter. An independently positive association between fruit and vegetable intake and BMD at the whole body (P = 0.005), lumbar spine (P < 0.001) and total hip (P = 0.024) remained even after adjusting for age, years since menopause, body weight and height, dietary energy, protein and Ca, and physical activities. A daily increase of 100 g fruit and vegetable intake was associated with 0.0062 (95 % CI 0.0019, 0.0105) g/cm2, 0.0098 (95 % CI 0.0041, 0.0155) g/cm2 and 0.0060 (95 % CI 0.0011, 0.0109) g/cm2 increases in BMD at the whole body, lumbar spine and total hip, respectively. In conclusion, greater fruit and vegetable intake is independently associated with better BMD among postmenopausal Chinese women.

Educational level and osteoporosis risk in postmenopausal Chinese women.

Many studies have shown that better education is favorable for lowering the risks for a number of chronic diseases, but little information is available on the relation with bone health. The authors examined the association of educational level, classified as levels I-IV, with bone mineral density (BMD) and with the prevalence of osteoporosis among 685 population-based, postmenopausal, Chinese women aged 48-63 years during 1999-2001. They observed a significant dose-response positive relation between educational level and BMDs at the total-body (p = 0.011), lumbar spine, and hip sites (p < 0.001) after adjusting for age, years since menopause, and body weight. Mean BMDs of educational level IV women were higher by 4.2-11.9% at the various sites compared with level I women (analysis of covariance, p < 0.05). Similarly, the authors also observed a significant inverse dose-response relation between educational level and prevalence of osteoporosis. Women of educational level I were 3.5-8.6 times more likely to be osteoporotic compared with those of level IV at the various sites. The proportion of BMD or osteoporosis variations accounted for by educational level was attenuated by about 40% after further controlling for potentially explanatory covariates. In conclusion, a higher level of education is independently associated with better BMDs and lower prevalence of osteoporosis among postmenopausal Chinese women.

High habitual calcium intake attenuates bone loss in early postmenopausal Chinese women: an 18-month follow-up study.

This study assessed the association of habitual dietary calcium intake and bone loss in early postmenopausal women. Four hundred fifty-four healthy postmenopausal Chinese women were enrolled for this 18-month cohort study. The subjects were 48-62 yr of age and within 12 yr of natural menopause. Dietary intake was assessed by the food frequency method, and bone mass was measured using dual energy x-ray absorptiometry at baseline and 9 and 18 months. The association between mean habitual dietary intake over the follow-up period and the rate of bone loss was examined. During the 18-month follow-up, the total loss rates of BMD at the whole body, lumber spine, femoral neck, and total hip were 1.28, 0.60, 1.54, and 0.56% (all P < 0.01). Subjects were stratified into four quartiles according to calcium intake during the period of follow-up. Quartiles I-IV had median intakes of 341, 505, 682, and 934 mg Ca/d. Subjects in quartile IV had significantly less BMD loss at the whole body and less BMD/bone mineral content loss at Ward's triangle, even after adjustments for confounding factors (by analysis of covariance). Multiple linear regression analyses showed significant positive associations between calcium intake and BMD change at the whole body (P = 0.006) and Ward's triangle (P = 0.021). Calcium intake was significantly associated with bone mineral content change at the trochanter (P = 0.025) and Ward's triangle (P < 0.001). No significant effect of calcium intake at the spine was found. In conclusion, habitual dietary calcium intake had a beneficial effect on bone loss at the whole body and some regions of the hip. Our findings suggest that an intake exceeding 900 mg calcium/d was helpful in the prevention of cortical bone loss among early postmenopausal Chinese women.

Beneficial effect of soy isoflavones on bone mineral content was modified by years since menopause, body weight, and calcium intake: a double-blind, randomized, controlled trial.

OBJECTIVE: Many studies have shown that soy isoflavones have an effect in preventing estrogen-related bone loss, but no data reported whether such an effect could be influenced by other important factors affecting bone loss. This study examines whether the associations between isoflavone supplementation and rates of change in bone mineral content (BMC) could be modified by years since menopause (YSM), body weight (BW), and dietary calcium intake in postmenopausal Chinese women aged 48 to 62 years. DESIGN: A group of 203 eligible women were randomly assigned to three treatment groups: placebo (daily dose of 0 mg isoflavones + 500 mg calcium, n = 67), mid-dose (40 mg isoflavones + 500 mg calcium, n = 68); and high-dose (80 mg isoflavones + 500 mg calcium, n = 68). Bone mineral density (BMD) and BMC at the whole body, spine, and hip were measured by dual-energy x-ray absorptiometry at baseline and posttreatment after 1 year. YSM, BW, and dietary calcium intake stratified analyses were performed to evaluate whether the associations between isoflavones supplementation and BMC change rates were varied with these factors. RESULTS: Both univariate and multivariate analyses observed significant favorable effect of isoflavone supplementation on rates of change in BMC at the total hip and trochanter among later postmenopausal women (> 4 y), in women with lower BW (< or =median, 55.5 kg), or among women with lower level of calcium intake (< or =median, 1095 mg/d). CONCLUSIONS: The independent effect of soy on the maintenance of hip BMC is more marked in women in later menopause or those with lower BW or calcium intake.

Soy isoflavones have a favorable effect on bone loss in Chinese postmenopausal women with lower bone mass: a double-blind, randomized, controlled trial.

Animal studies have shown that soy isoflavones have an effect in preventing estrogen-related bone loss, but few data are available in humans, especially in the Asian populations. This double-blind, placebo-controlled, randomized trial examines the effects of soy isoflavones on bone loss in postmenopausal Chinese women, aged 48-62 yr. Two hundred and three eligible subjects were randomly assigned to three treatment groups with daily doses of placebo (1 g starch; n = 67), mid-dose (0.5 g starch, 0.5 g soy extracts, and approximately 40 mg isoflavones; n = 68), and high dose (1.0 g soy extracts and approximately 80 mg isoflavones; n = 68). All were given 12.5 mmol (500 mg) calcium and 125 IU vitamin D(3). Bone mineral density (BMD) and bone mineral content (BMC) of the whole body, spine, and hip were measured using dual energy x-ray absorptiometry at baseline and 1 yr post treatment. Both univariate and multivariate analyses showed that women in the high dose group had mild, but statistically significantly, higher favorable change rate in BMC at the total hip and trochanter (P < 0.05) compared with the placebo and mid-dose groups, even after further adjustments for the potential confounding factors. Further stratified analyses revealed that the positive effects of soy isoflavone supplementation were observed only among women with lower initial baseline BMC (median or less). In conclusion, soy isoflavones have a mild, but significant, independent effect on the maintenance of hip BMC in postmenopausal women with low initial bone mass.

Homocysteine, endothelial dysfunction, and coronary artery disease: emerging strategy for secondary prevention.

Atherosclerosis is an important medical problem of the 21st century, but traditional risk factors could only account for 50% of the problem. Hyperhomocysteinemia is emerging as an independent atherosclerosis risk factor, associated with folate deficiency, renal failure, and relative deficiency of MTHFR (C677T polymorphism) or other enzymes depending on gender, age, and smoking status. Hyperhomocysteinemia has been reported to occur in 11-22% of western people, in 3-5% of normal asymptomatic Chinese subjects aged 18-70 years in Hong Kong, Macau, Sydney, and San Francisco, 23-36% of Chinese in Hong Kong with premature coronary artery disease, and 29% of a nonselective series of coronary subjects in Hong Kong. Evidence is accumulating that documents its associations with atherosclerosis disease in both case-control observations and prospective cohort studies, in vitro experiments, and in vivo experimental models in both animals and human subjects, as well as the successful improvement by homocysteine-lowering of endothelial function as surrogate atherosclerosis endpoints in asymptomatic human and coronary patients (secondary prevention). A number of large scale homocysteine-lowering trials are currently underway for stroke and heart attacks prevention. Collectively these trials will include more than 65,000 patients at high-risk for cardiovascular and stroke events, and should provide a reliable evidence-base for prevention.